Surveillance Study of Influenza Occurrence and Immunity in a Wisconsin Cohort During the 2009 Pandemic

Abstract

Background.Antibody and T-cell immunity to conserved influenza virus antigens can protect animals against infection with diverse influenza strains. Although immunity against conserved antigens occurs in humans, whether such responses provide cross-protection in humans and could be harnessed as the basis for universal influenza vaccines is controversial. The 2009 pandemic provided an opportunity to investigate whether pre-existing cross-reactive immunity affected susceptibility to infection.Methods.In 2009, we banked sera and peripheral blood mononuclear cells (PBMC) from blood donors, then monitored them for pandemic influenza infection (pH1N1) by polymerase chain reaction or seroconversion. Antibodies to hemagglutinin (HA), neuraminidase (NA), nucleoprotein (NP), matrix 2 (M2), and HA-pseudotypes were measured in sera. T-cell inteferon-γ enzyme-linked immunospot responses were measured in PBMC.Results.There were 13 infections in 117 evaluable donors. Pre-existing T-cell reactivity to pH1N1 was substantial (of 153 donors tested, 146 had >100 spot-forming cells/106 cells). Antibodies reactive with pH1N1 were common: anti-NP (all donors) and anti-M2 (44% of donors). Pseudotype-neutralizing antibodies to H1 were detected, but not to highly conserved HA epitopes. Unexpectedly, donors with symptomatic pH1N1 infection had sharp rises in HA pseudotype-neutralizing antibodies, not only pH1N1 but also against multiple seasonal H1s. In addition, an exploratory study of a T-cell marker (response to NP418-426) identified probable infection missed by standard criteria.Conclusions.Although the number of infections was inadequate for conclusions about mechanisms of protection, this study documents the wide variety of pre-existing, cross-reactive, humoral and cellular immune responses to pandemic influenza virus antigens in humans. These responses can be compared with results of other studies and explored in universal influenza vaccine studies.

The effect of respiratory viruses on immunogenicity and protection induced by a candidate universal influenza vaccine in mice

“…Antibody responses to M2e are weak and variable in mice following influenza virus infection or immunization with cold-adapted influenza virus [1, 4,48–50]. Similarly, in humans, induction of an M2e-specific antibody response following influenza infection is highly variable [51–53]. In agreement with those findings, an M2e-specific antibody response was not induced by A/Udorn infection followed by B/NP-rAd immunization (Fig 1D).…”

More Than Just Gene Therapy Vectors: Lentiviral Vector Pseudotypes for Serological Investigation

“…Influenza virus requires constant surveillance at the human–animal interface to identify the emergence of new subtypes and help guide seasonal vaccination campaigns, as well as monitoring population immunity. To this effect, pseudotyped LVs have been used in multiple studies [ 70 , 71 , 72 , 73 , 74 ]. The flexibility to incorporate different reporter genes within the LV was exploited in one study to produce a multiplex assay, simultaneously detecting NAbs against a H5 and H7 subtype in serum collected from vaccinated chickens [ 102 ].…”